Mercury Toxicity

Article Author:
Shawn Posin
Article Editor:
Sandeep Sharma
Updated:
10/27/2018 12:31:56 PM
PubMed Link:
Mercury Toxicity

Introduction

Mercury has been used for centuries in multiple capacities including medicinal and widespread industrial use. Because of this, it is a common chemical exposure and environmental pollutant. There are several forms of mercury which lead to different mercury intoxication syndromes.

Etiology

Mercury exists in organic and inorganic forms. The inorganic form could be further subdivided into elemental mercury (also known as "quicksilver") and mercury salts. Elemental exposures are typically from mercury-containing devices such as thermometers. Mercury salt exposures can be seen with disc battery ingestion or laxative abuse. Organic mercury can also be subdivided into short-chain and long-chain compounds. Organic mercury exposure usually occurs from ingestion of contaminated seafood, paints containing mercury, or ingestion/injections of thimerasol.

Epidemiology

In the United States, a 2013 report documented 1300 single mercury exposures, and only 24 had moderate to major effects. However, internationally, there are much higher rates of exposure including mercury mining in China, small-scale gold mining, and food contaminated with mercury. Two major toxic incidents occurred in Minamata Bay, Japan and in Iraq. Mercury was dumped into Minamata Bay, and members in the community developed toxicity from eating the fish containing methylmercury. In Iraq, over 6000 people developed toxicity from eating bread baked with grain that was treated with methylmercury based fungicide.

Children and fetuses have a higher susceptibility to mercury toxicity, and therefore, more severe clinical manifestations. The primary source of dietary ingestion is consumption of contaminated fish. Since the fetal brain is more susceptible to toxicity, the FDA recommends pregnant or breastfeeding women, as well as children, avoid fish with high mercury content. These fish include shark, king mackerel, tilefish, swordfish, and tuna. Freshwater fish including pike, walleye, muskellunge, and bass should be eaten in moderation.

Pathophysiology

Elemental mercury is primarily absorbed by inhalation. There is minimal absorption through ingestion, and it does cross the blood-brain barrier where it can deposit. Elemental mercury is more volatile as it is heated and is readily absorbed when it is aerosolized by vacuuming. Pulmonary, central nervous system (CNS), and renal toxicity are common with elemental mercury. The gastrointestinal tract primarily absorbs inorganic mercury salts, and secondarily they are absorbed through intact skin. The salts mainly cause renal and gastrointestinal (GI) toxicity. Organic mercury is also primarily absorbed by the GI tract and secondarily through intact skin.  Organic mercury toxicity typically leads to neurologic symptoms which are characteristically delayed.

Histopathology

Mercury primarily binds to sulfhydryl groups and secondarily to an amide, carboxyl, and phosphoryl groups which interrupt cellular enzymes and protein systems throughout the body. Therefore, mercury can cause significant dysfunction of enzymes, membranes, transport mechanisms, and structural proteins. Inhibition of enzymes such as choline acetyltransferase and catechol O-methyltransferase can lead to acetylcholine deficiency, hypertension, and tachycardia. Mercury salts cause damage to the gastrointestinal tract mucosa and proximal renal tubules early after exposure. This damage is from direct oxidative effects of mercuric ions. Inorganic salts have low lipid solubility, so they have a poor penetration of the blood-brain barrier, but due to slow elimination, there is some accumulation. Organic mercury such as methylmercury is lipophilic and distributes across all tissues including the central nervous system. The organic mercury deposits in the CNS are thought to be converted to inorganic mercury causing toxicity. Neurologic findings on MRI of atrophy of the cerebellar hemisphere, postcentral gyri, and calcarine area correlates with ataxia, sensory neuropathy, and visual field constriction.

Toxicokinetics

Excretion of mercury is dependant on its original form. Elemental and inorganic salts are primarily excreted through the kidney and minimally through the GI tract with a total half-life of 30 to 60 days. Excretion of organic mercury compounds is primarily fecal with enterohepatic recirculation leading to a longer half-life of approximately 70 days.

History and Physical

Primary absorption of elemental mercury is through inhalation which causes shortness of breath, cough, fever, nausea, vomiting, diarrhea, headache, metallic taste, salivation, and visual disturbance. Severe exposure may lead to respiratory distress and failure. Ingested elemental mercury can be metabolized to inorganic mercury salts and can also develop those symptoms. Acute ingestion of organic salts typically will cause a metallic taste and a graying of the oral mucosa. Most common findings of significant ingestion include abdominal pain, hemorrhagic gastroenteritis, acute tubular necrosis, and shock. Subacute mercury salt ingestion can lead to a wide array of GI, neurologic, and renal symptoms including loose teeth, salivation, burning sensation in the mouth, tremors, erethism, nephrotic syndrome, proteinuria, neurasthenia, and acrodynia. Organic mercury toxicity is primarily neurologic and is usually permanent. The related toxic symptoms typically occur weeks to months after exposure. Early findings of orofacial paresthesias, headaches, tremors, and fatigue can occur. More severe cases can progress to ataxia, blindness, movement disorders, and dementia. In addition to the severe neurologic findings, patients also develop mild renal, GI, and respiratory distress.

Evaluation

In the Emergency Department, the most critical facet of the evaluation is a thorough history including possible exposures and identifying the symptoms consistent with any of the mercury toxicity syndromes.  Initial testing would include a chest radiograph, urinalysis,  and basic bloodwork such as a complete blood count and a metabolic panel.  A 24-hour urine collection for mercury levels should be obtained as well as whole-blood mercury levels in the case of organic mercury exposure as there is very little urinary excretion of these compounds.  Positive levels confirm exposure, but the levels do not directly correlate with toxicity.

Treatment / Management

Initial treatment in the emergency department consists of removal from the exposure and decontamination of the patient. After the patient and department are safe from the exposure supportive measures should begin including oxygen and intravenous (IV) fluids. Monitor and manage any complications of the toxicity such as respiratory distress, gastrointestinal bleeding, renal failure, and bowel perforation. GI decontamination should be attempted if possible although there are risks of perforation. Charcoal which is not highly effective binding metals should still be attempted, in addition to whole bowel irrigation even if only minimally effective. Chelation should be initiated early in mercury exposure cases as it may decrease the toxic effects. Inorganic mercury and elemental mercury can be treated with an initial course of intramuscular dimercaprol and then followed by oral succimer. The dosing regimen for dimercaprol starts at 5 mg/kg per dose every 4 hours for 48 hours, followed by 2.5 mg/kg per dose every 6 hours for 48 hours, and then 2.5 mg/kg per dose every 12 hours for 7 days. Oral succimer follows this treatment at a dose of 10 mg/kg per dose orally 3 times a day for 5 days then twice daily for 14 days. Organic exposures should not be treated with dimercaprol as there is evidence it can exacerbate neurologic toxicity.  In these cases, the only succimer should be administered. It is controversial whether peritoneal dialysis or hemodialysis is beneficial due to the high degree of protein binding and distribution; although dialysis may be necessary due to renal damage. In addition, exchange transfusions should be attempted, but there is no supporting evidence of improved outcomes.

Differential Diagnosis

Mercury toxicity can be very difficult to diagnose due to nonspecific signs and symptoms and the variability of onset of the symptoms.  These can easily mimic several other disease processes affecting multiple systems including renal, gastrointestinal, nervous, and pulmonary.  Which is why it is imperative to obtain a complete, thorough history.  A differential diagnosis includes the following list.

Alzheimer disease, senile dementia, Parkinson disease, CVA, cerebellar tumor, metabolic encephalopathy, gastrointestinal bleed, acid or alkali ingestion, iron toxicity, arsenic toxicity, phosphorus toxicity, cerebral palsy, vertigo, amyotrophic lateral sclerosis, intrauterine hypoxia, brainstem gliomas, carbon monoxide poisoning, and alcohol or drug withdrawal.  

Prognosis

The prognosis for mercury exposure is highly variable but is dependant on the level of exposure. Significant exposures can lead to coma and death. Minor symptoms may resolve over time. Neurologic symptoms which can be delayed in the presentation may persist for decades. Fetus and children are highly susceptible and can lead to death, permanent neurologic deficits, or mental retardation.

Pearls and Other Issues

Mercury toxicity can be very difficult to identify with multisystem involvement. It is imperative to have a high index of suspicion and obtain a thorough history while always keeping in mind the complex of symptoms found in the toxidromes. Symptoms of mercury exposure and toxicity can easily be misdiagnosed as normal medical problems such as gastritis, GI bleeding, and respiratory distress. A keen awareness leading to early identification and treatment is critical due to the severe and potentially irreversible damage.